Synthesis of some novel 5-substituted benzamido-6-arylamino-pyrazolo[3,4-D]pyrimidin-4-one derivatives for herbicidal activity

Abstract

Sixteen novel 3-methylthio-5-substituted benzamido-6-arylamino-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4 (5H)-one derivatives (4a–p) were successfully synthesized from iminophosphoranes, aryl isocyanate, and substituted benzoylhydrazine. The structures of the title compounds were elucidated by FT-IR, ¹H NMR, ¹³C NMR, and HRMS. Herbicidal activity of the compounds 4a–p against Brassica napus (rape), Echinochloa crusgalli (barnyard grass), Cucumis sativus (cucumber), and Triticum aestivum (wheat) were determined. The results showed that 5-(2-chlorobenzamido)-6-phenylamino-3-methylthio-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4 (5H)-one (4c) displayed remarkable inhibition activity against the stalk and root of rape with 100% inhibition rate at the dosages of 10?mg/L and 100?mg/L, and 5-(4-nitrobenzamido)-6-phenylamino-3-methylthio-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4 (5H) -one (4d) exhibited excellent activity against the stalk and root of barnyard grass with 100% inhibition rate at the same dosages.     

SYNTHESIS AND FUNGICIDAL ACTIVITIES OF 2-BENZOTHIAZOLYLTHIO-SUBSTITUTED 4H-IMIDAZOL-4-ONES AND 4(3H)-QUINAZOLINONES

4H-Imidazol-4-ones 4 or 4(3H)-quinazolinones 8 were synthesized by base catalytic reactions of 2-mercaptobenzothiazole with carbodiimides 2 or 6, respectively, which were obtained via aza-Wittig reaction of iminophosphorane 1 or 5 with aromatic isocyanates. 4 and 8 exhibited fungicidal activity.     

Crystal and Molecular Structure of 4-Nitro-2-oximino-3-phenylamino-3-thiolene-1,1-dioxide

The present publication reports the results of X-ray diffraction (XRD) analysis of 4-nitro-2-oximino-3-phenylamino-3-thiolene-1,1-dioxide crystals (I). The synthesis and the useful properties of this class of compounds are reviewed in [1]. It is noteworthy that previously [2] an X-ray structure analysis has been performed for another compound from this class, 3-methyl-4-nitro-2-oximino-3-thiolene-1,1-dioxide (II), which was assumed to exist in nitrone form. The XRD data for compound I disprove this assumption.     

Reaction of Dimethyl Sulfoxide with 4-Acyloxycoumarins

Dimethyl sulfoxide converts 4-acetoxycoumarin (1) exclusively to 2-(2-hydroxybenzoyl)-2-[(methylthio)methyl]-2,3-dihydro-4 H-furo[3,2-c]chromen-4-one (3) at 180°C under a nitrogen atmosphere, but in the absence of nitrogen, the products obtained are dicoumarol and its dehydrative cyclization products 7 H-bis[1]benzopyrano[4,3-b: 3′,4′-c]pyran-6,8-dione (9) and (3). Under similar conditions, 4-benzoyloxycoumarin (1a) affords benzoic acid, 4-hydroxy-3-({2-[(methylthio)methyl]-3-oxo-2,3-dihydro-1-benzofuran-2-yl}methyl)-2H-chromen-2-one (7), and 3-(2-hydroxybenzoyl)-3,4-dihydro-2H,5H-pyrano[2,3-b] chromen-5-one (8).     

Synthesis and Characterization of New Thiazolidin-4-one Derivatives

The synthesis of some new functionalized thiazolidin-4-one derivatives has been described. The N-substituted-thiosemicarbazides 3a-3i were obtained though the reaction of alkylamines 2a–2i , carbon disulfide, and hydrazine hydrate. The condensation reaction between 3a–3i and 4-amino-2-methanesulfanylpyrimidine-5-carboxaldehyde 1 afforded the thiosemicarbazones 4a–4i . The corresponding thiazolidin-4-ones 5a–5i were prepared by cyclization of 4a–4i with ethyl bromoacetate. The structures of the final products were confirmed by IR, ¹ H NMR, ¹³ C NMR, and HRMS.     

3-(4-吡啶基)-4-(6-取代色酮-3-基-亚甲氨基)-5-芳氨基-1,2,4-三唑的合成

N-芳基-N'-[(4-吡啶基)羰基]氨基硫脲用85%的水合肼环化, 得到3-(4-吡啶基)-4-氨基-5-芳氨基-1,2,4-三唑(2a～2c). 然后再与3-甲酰基色酮(3a～3d)反应, 制备得到了一系列新化合物: 3-(4-吡啶基)-4-(6-取代色酮-3-基亚甲氨基)-5-芳氨基-1,2,4-三唑(4a～4c, 5a～5c, 6a～6c, 7a～7c). 化合物的结构经元素分析, IR, ¹H NMR和MS确证.     

UNPRECEDENTED OUTCOME OF BASE-PROMOTED NEBER REARRANGEMENT OF O-MESYLOXIME OF 2-ARYL-1,2,3,4-TETRAHYDRO-1-METHYLSUL FONYL-4-QUINOLONE- SYNTHESIS OF 4-AMINO-2-ARYLQUINOLINES

Abstract

O-Mesyloximes derived from 2-aryl-1,2,3,4-tetrahydro-1-methylsulfonyl-4-quinolones react with sodium ethoxide in ethanol to afford the 4-amino-2-arylquinolines in high yield. No traces of the 3-amino-2-aryl-4-quinolones expected from the Neber rearrangement of the substrates were detected or isolated from the reaction mixture. The structures of the products were determined using a combination of ¹H NMR, ¹³C NMR, IR and mass spectroscopic techniques.     

Synthese von 4H-Pyrano[2,3-d]pyrimidinen

Summary Good yields of substituted 5-(5R-2-furyl)-4H-pyrano[2,3-d]pyrimidines4 were obtained in the reaction of 2-ethoxymethyleneamino-3-cyano-4H-pyranes2 with ammonia. Compounds2 were prepared by the condensation of the starting 2-amino-5-acetyl-3-cyano-6-methyl-4H-pyranes1 with ethyl orthoformate. Spectral properties of the bicyclic system4 in relation to compounds3 are discussed.

     

SYNTHESIS AND CHEMISTRY OF SOME NEW 2-MERCAPTOIMIDAZOLE DERIVATIVES OF POSSIBLE ANTIMICROBIAL ACTIVITY

4,5-Diaryl-2,3-dihydro-2-mercaptoimidazoles (2a–e) were synthesized. They reacted with chloroacetic acid in gl. acetic acid/Ac ₂ O in presence of anhyd. sodium acetate afforded 5,6-diaryl-2,3-dihydro-imidazo[2,1-b]thiazol-3-ones (3a–d). Also these compounds were prepared by the action of chloroacetyl chloride on compounds (2) in pyridine. Compounds (3a–d) on condensation with aromatic aldehydes yield 2-arylmethylene-5,6-diaryl-2,3-dihydroimidazo[2,1-b]-thiazol-3-ones (4a–q). The latter compounds were prepared directly by the reaction of (2) with chloroacetic acid and the aromatic aldehydes. Compounds (3a–d) coupled with aryldiazonium salts in pyridine to give 2-arylhydrazono-5,6-diaryl-2,3-dihydroimidazo[2,1-b]thiazol-3-ones (5a–r). Also compounds (2) when reacted with 2 or 3-bromopropionic acid afford 2,3-di-hydro-5,6-diaryl-2-methylimidazo[2,1-b]thiazol-3-ones (6a–d) and 2,3-di-hydro-6,7-diaryl imidazo-[2,1-b]-1,3-thiazin-4-ones (7a–d), respectively. Compounds (3, 6, and 7) have been cleaved by aromatic amines to give the corresponding 2-(4′,5′-diaryl-2′,3′-dihydroimidazol-2′-yl)thioacetanilide (8a–f), 2-(2′,3′-dihydro-4′,5′-diaryl imidazol-2′-yl)thiopropionamide (9a–c), and 3-(2′,3′-dihydro-4′,5′-diaryl-imidazol-2′-yl)thiopropionamide (10a–d) respectively. All the prepared compounds show considerable antimicrobial activity against bacteria, yeast, and fungi.     

4-Phosphoranylidene-5(4H)-oxazolones — A novel synthesis and properties

Summary 4-Phosphoranylidene-5(4H)-oxazolones (2), a hardly known class of phosphorus ylides, were readily prepared from 4-unsubstituted-5-(4H)-oxazolones (1) by treatment with Ph₃P-Br₂, Bu₃P-Br₂, Ph₃P-CCl₄, or Ph₃P-CBr₄ adducts in the presence of triethylamine in CH₂Cl₂ at room temperature in a novel, efficient one-pot procedure. The spectroscopic properties of the ylides are reported and discussed.

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4-Phosphoranyliden-5(4H)-oxazolone — Eine neue Synthese und Eigenschaften

Zusammenfassung 4-Phosphoranyliden-5(4H)-oxazolone, eine sehr wenig bekannte Gruppe der Phosphor-ylide, wurden auf einfache Weise nach einem neuen Eintopfverfahren mit guten Ausbeuten hergestellt. Als Ausgangsverbindungen wurden 4-unsubtituierte-5-(4H)-Oxazolone (1) eingesetzt, die unter der Einwirkung von Addukten wie Ph₃P-Br₂, Bu₃P-Br₂, Ph₃P-CCl₄ oder Ph₃P-CBr₄ in Anwesenheit von Triethylamin in CH₂Cl₂ bei Zimmertemperatur die Titelverbindungen liefern. Die spektroskopischen Eigenschaften der Ylide werden berichtet und diskutiert.

     

N-(6-色酮-3-基-亚甲氨基)-S-{[4-芳基-5-(吡啶-4-基)]-1,2,4-三唑-2-基}巯乙酰胺类化合物的合成

N-芳基-2-[(吡啶-4-基)羰基]氨基硫脲1a～1e用NaOH溶液环合, 得到3-巯基-4-芳基-5-(吡啶-4-基)-1,2,4-三唑(2a～2e), 经酯化, 肼解, 得S-{[4-芳基-5-(吡啶-4-基)]-1,2,4-三唑-3-基}巯乙酰肼(3a～3e), 再与3-甲酰基色酮(4a～4d)反应, 合成得到了一系列新化合物5a～5e, 6a～6e, 7a～7e, 8a～8e. 化合物的结构经元素分析, IR, ¹H NMR和MS谱确证.     

Facile Synthesis of Some New Pyrazole-Based 2-Thioxo-4-thiazolidinone

5-Ethoxymethylene-2-thioxo-4-thiazolidinone (1) reacts with hydrazine hydrate at room temperature to afford 5-(hydrazinylmethylene)-2-thioxo-4-thiazolidinone (3). Compound 3 condensed with different aromatic aldehydes 6a–d in ethanol in the presence of a few drops of piperidine to give the corresponding Schiff’s bases 7a–d. On the other hand, compound 3 reacts with o-hydroxybenzaldehyde derivatives 8a and 8b in refluxing ethanol catalyzed by a few drops of piperidine to yield 1H-inadzolyl-2-thioxo-4-thiazolidinones 9a and 9b. Reaction of compound 3 with α-ketoesters 10a and 10b or α-diketones 10c–e in refluxing glacial acetic acid furnished the pyrazolyl-2-thioxo-4-thiazolidinone derivatives 11a–e. Also, compound 3 reacts with some different enaminones 12a–f in refluxing glacial acetic acid to afford the new pyrazolyl-2-thioxo-4-thiazolidinone derivatives 13a–f. Pyrazoles 15a–d was obtained via reaction of compound 3 with chalcones 14a–d in dimethylformamide (DMF). The structures of all the newly synthesized products were confirmed on the basis of their elemental and spectral data, and a plausible mechanism has been postulated to account for their formation.     

Über die Dicyanierung der 1,4-Diaminoanthrachinone und die Reaktivität der 1,4-Diamino-9,10-dihydroanthracen-2,3-dicarbonitrile gegenüber nucleophilen Reagenzien 3. Mitteilung über Arylierungen und Heterocyclisierungen von Anthrachinonsystemen

The Dicyanation of 1,4-Diaminoanthraquinones and the Reactivity of 1,4-Diamino-9,10-dioxo-9,10-dihydroanthracene-2,3-dicarbonitriles towards Nucleophilic Reagents The reaction of 1-amino-9, 10-dioxo-4-phenylamino-9,10-dihydroanthracene-2-sulfonic acid ( 1 , R?C₆H₅) with cyanide in water yields a mixture of 1-amino-9,10-dioxo-4-phenylamino-9,10-dihydroanthracene-2-carbonitrile ( 3 , R ? C₆H₅) and 1-amino-4-(phenylamino)anthraquinone ( 4 , R ? C₆H₅) under the usual reaction conditions (Scheme 1). In dimethylsulfoxide, however, a second cyano group is introduced, and 1-amino-9,10-dioxo-4-phenylamino-9,10-dihydroanthracene-2,3-dicarbonitrile (7) is formed (Scheme 2). The cyano groups are very reactive towards nucleophiles. The cyano group in 2-position can be substituted by hydroxide and aliphatic amines (Schemes 5 and 6). The cyano group in 3-position can be eliminated by aliphatic amines and hydrazine (Scheme 7). Nucleophilic attack at the cyano C-atom of the 2-cyano group by suitable reagents leads to ring formation, yielding e.g. 2-(Δ²-1, 3-oxazolin-2-yl)-, 2-(benz[d]imidazol-2-yl)- and 2-(1H-tetrazol-5-yl)anthraquinones (Schemes 8 and 10).     

PHOSPHONOMETHYLATION OF AMINOALKANOLS PREPARATION OF 4-(PHOSPHONOMETHYL)-2-HYDROXY-2-OXO-1,4,2-OXAZAPHOSPHORINANES1

Abstract

Treatment of aminoalkanols 1 with phosphorous acid and formaldehyde in presence of conc. hydrochloric acid gave mixtures of [(2-hydroxy alkyl)imino] dimethylene diphosphonic acids 3 and 4-(phosphonomethyl)-2-hydroxy-2-oxo-1,4,2-oxazaphosphorinanes 2 from which 2 were isolated as crystalline solids. Similar treatment of 2-amino-2-methyl-1,3-propanediol 8 gave a complex mixture from which dimethylene diphosphonic acid of 5-amino-5-methyl-1,3-dioxane 9 was isolated. 2-Aminoethanethiol, when subjected to phosphonomethylation. gave an unexpected novel quarternary nitrogen product 11. N-Alkylaminoalkanols 4 on phosphonomethylation gave 3:1 mixtures of [N-alkyl-N-(2-hydroxyalkyl)amino] methane phosphonic acid 6 and N-alkyl-2-hydroxy-2-oxo-1,4,2-oxazaphosphorinane 5. Treatment of the crude mixtures of 5 and 6 with aqueous sodium hydroxide gave disodium salts of [N-alkyl-N-(2-hydroxyalkyl)amino] methanephosphonic acid 7. The ratio of the cyclic to the open chain structures obtained as well as the formation of any unexpected novel products is dependent on the structure of the aminoalkanol that is phosphonomethylated. The ¹H, ¹³C and ³¹P spectra are reported for all new compounds.     

Synthesis of substituted 4H-thiazolo[4,5-b][1]benzothiopyran-4-ones as possible schistosomicidal agents

Summary Interaction of ethyl 2-acetamido-5-bromothiazole-4-carboxylate (2) with 2-methyl-5-chlorothiophenol (3) afforded the thioether4, which was hydrolysed to the corresponding carboxylic acid5. Attempted cyclization of5 to6 yielded the decarboxylated product7. On the other hand, interaction of 2-acetamido-5-bromothiazole (9) with thiosalicylic acid (10) yielded the thioether11, which was cyclized to compound12. Acid hydrolysis of12 yielded the amino derivative13, which was reacted with certain selected alkyl halides using sodium hydride to afford compounds14–18.

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Synthese von substituierten 4H-Thiazolo[4,5-b][1]benzothiopyran-4-onen als mögliche schistosomicide Wirkstoffe

Zusammenfassung Die Reaktion von Ethyl 2-Acetamido-5-bromthiazol-4-carboxylat (2) mit 2-Methyl-5-chlorthiophenol (3) ergab den Thioether4, der zur entsprechenden Carbonsäure5 hydrolysiert wurde. Die versuchte Cyclisierung von5 zu6 ergab das Decarboxylierungsprodukt7. Andererseits ergab die Reaktion von 2-Acetamido-5-bromthiazol (9) mit Thiosalizylsäure (10) den Thioether11, der zu Verbindung12 cyclisiert werden konnte. Saure Hydrolyse von12 ergab das Aminoderivat13, das mit geeigneten Alkylhalogeniden unter Verwendung von Natriumhydrid zu den Verbindungen14–18 führte.

     

Synthesis and antiemetic activity of 1,2,3,9-tetrahydro-9-methyl-3-(4-substituted-piperazin-1-ylmethyl)-4H-carbazol-4-one derivatives

5-HT₃ receptor antagonists, such as Ondansetron, are used for anti-emesis after chemotherapy, radiotherapy and operations. Some Ondansetron analogs possessing piperazine ring as side chains were synthesized in our lab. Thus, one of the two carbonyl groups of starting material 1,3-cyclohexandione (1) was condensed with phenylhydrazine hydrochloride to form monophenylhydrazone (2). 1,2,3,9-Tetrahydro-4H-carbazol-4-one (3) was prepared from 2 via cyclization and rearranged in the presence of ZnCl₂. Through a methylation reaction, compound 3 was converted to 1,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one (4). 3-Dimethylaminomethyl substituted compound (5) was synthesized from 4 by a Mannich reaction in glacial acetic acid. Nine novel 1,2,3,9-tetrahydro-9-methyl-3-(4-substituted-piperazin-1-ylmethyl)-4H-carbazol-4-one derivatives (6a–6i) were synthesized through nucleophilic substitution reaction of 5 with piperazines. The structures of all the target compounds were determined by elemental analysis, IR, MS, ¹H NMR and ¹³C NMR spectra. The results of preliminary pharmacological test show that part of the novel compounds have antiemetic activity comparable to that of the control Ondansetron. __________ Translated from Chinese Journal of Organic Chemistry, 2008, 28(2) (in Chinese)     

Synthesis and structure of the products of the reactions of 3-chloro-5-methoxy-4-[(4-methylphenyl)sulfanyl]-2(5H)-furanone with N,N-binucleophilic agents

Reactions of 3-chloro-5-methoxy-4-[(4-methylphenyl)sulfanyl]-2(5H)-furanone with different nitrogen-containing binucleophilic agents were studied. The reaction with hydrazine monohydrate resulted in the formation of 1,5-dihydro-2H-pyrrol-2-one and pyridazin-3(2H)-one derivatives, whereas the reaction with phenylhydrazine led exclusively to 1-phenylamino-1,5-dihydro-2H-pyrrol-2-one. The reaction with ethylenediamine resulted in the isolation of 1,2-bis[2-oxo-1,5-dihydro-2H-pyrrol-1-yl]ethane: the enantiomeric dl-pair and two poly-morphic modifications of meso-form, which were characterized by X-ray crystallography.     

1-苯基-3-芳基-4-甲酰基吡唑衍生物的合成及其荧光性能

以苯肼和4-取代苯乙酮(1a～1d)为原料, 经过缩合, 再与Vilsmeier-Haak试剂反应合环, 制得1-苯基-3-芳基-4-甲酰基吡唑(3a～3d), 将其与2-肼基-4/6-取代苯并噻唑(4a～4f)反应, 合成一系列新化合物1-苯基-3-芳基-吡唑-4-醛 [N-(4/6-取代苯并噻唑-2-基)]腙5～8. 所有新化合物的结构均经IR, ¹H NMR, MS谱和元素分析证实. 对化合物5～8的荧光进行了测定, 结果显示这些化合物具有荧光特性, 并探讨了化合物的结构对荧光性能的影响.     

Synthesis of pyridinyl-4-pyrimidinamine derivatives

Summary N-(1-Methyl-2-pyridin-3(4)-yl-vinyl)acetimidoylchlorides (5, prepared byBeckmann rearrangement of the oximes of 3-methyl-4-pyridin-3(4)-yl-3-buten-2-ones (4)) react with cyanamide and N,N-dialkylcyanamides in the presence of titanium(IV) chloride to give 4-amino-2,6-dimethyl-5-pyridinyl-pyrimidine derivatives (7).

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Synthese von Pyridinyl-4-pyrimidinamin-Derivaten

Zusammenfassung N-(1-Methyl-2-pyridin-3(4)-yl-vinyl)acetimidoyl-chloride (5, dargestellt durchBeckmann-Umlagerung der Oxime von 3-Methyl-4-pyridin-3(4)-yl-3-buten-2-onen (4)) reagieren mit Cyanamid und N,N-Dialkylcyanamid in Gegenwart von Titan(IV)chlorid zu 4-Amino-2,6-dimethyl-5-pyridinyl-pyrimidin-Derivaten (7).